Kavanagh Edel T, Loughlin John P, Herbert Kate Reed, Dockery Peter, Samali Afshin, Doyle Karen M, Gorman Adrienne M
Department of Biochemistry, National University of Ireland, Galway, Ireland.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):890-5. doi: 10.1016/j.bbrc.2006.10.104. Epub 2006 Oct 30.
6-Hydroxydopamine (6-OHDA) is often used in models of Parkinson's disease since it can selectively target and kill dopaminergic cells of the substantia nigra. In this study, pre-treatment of PC12 cells with nerve growth factor (NGF) inhibited apoptosis and necrosis by 6-OHDA, including caspase activity and lactate dehydrogenase release. Notably, cells exposed to 6-OHDA in the presence of NGF were subsequently capable of proliferation (when replated without NGF), or neurite outgrowth (with continued presence of NGF). Following 7 days growth in the presence of NGF, expression of betaIII tubulin and tyrosine hydroxylase and increased intracellular catecholamines was detectable in PC12 cells, features characteristic of functional dopaminergic neurons. NGF-pre-treated PC12 cells retained expression of betaIII-tubulin and tyrosine hydroxylase, but not catecholamine content following 6-OHDA exposure. These data indicate that NGF-protected cells maintained some aspects of functionality and were subsequently capable of proliferation or differentiation.
6-羟基多巴胺（6-OHDA）常用于帕金森病模型，因为它可以选择性地靶向并杀死黑质中的多巴胺能细胞。在本研究中，用神经生长因子（NGF）预处理PC12细胞可抑制6-OHDA诱导的细胞凋亡和坏死，包括半胱天冬酶活性和乳酸脱氢酶释放。值得注意的是，在NGF存在下暴露于6-OHDA的细胞随后能够增殖（当在无NGF的情况下重新接种时）或长出神经突（在持续存在NGF的情况下）。在NGF存在下生长7天后，在PC12细胞中可检测到βIII微管蛋白和酪氨酸羟化酶的表达以及细胞内儿茶胺增加，这些是功能性多巴胺能神经元的特征。经NGF预处理的PC12细胞在暴露于6-OHDA后保留了βIII-微管蛋白和酪氨酸羟化酶的表达，但儿茶胺含量未保留。这些数据表明，NGF保护的细胞维持了某些功能方面，随后能够增殖或分化。
